Abstract
ObjectivePatients with diabetes mellitus have an increased risk of fractures; however, the underlying mechanism is largely unknown. We aimed to investigate whether the risk of major osteoporotic fractures in diabetes patients differs between subjects initiated with alendronate and denosumab, respectively.Methods and Research DesignWe conducted a retrospective nationwide cohort study through access to all discharge diagnoses (ICD-10 system) from the National Danish Patient Registry along with all redeemed drug prescriptions (ATC classification system) from the Health Service Prescription Registry. We identified all subjects with a diabetes diagnosis between 2000 and 2018 and collected data on the first new prescription of anti-osteoporotic treatment between 2011 and 2018. Exposure was defined as either alendronate or denosumab treatment initiated after diabetes diagnosis. Outcome information was collected by identification of all major osteoporotic fracture (MOF) diagnoses, i.e., hip, spine, forearm, and humerus, from exposure until 2018 or censoring by emigration or death. The risk of fracture was calculated as hazard ratios (HR) using multiply adjusted Cox proportional models with death as a competing risk.ResultsWe included 8,745 subjects initiated with either alendronate (n = 8,255) or denosumab (n = 490). The cohort consisted of subjects with a mean age of 73.62 (SD ± 9.27) years, primarily females (69%) and suffering mainly from type 2 diabetes (98.22%) with a median diabetes duration at baseline of 5.45 years (IQR 2.41–9.19). Those in the denosumab group were older (mean 75.60 [SD ± 9.72] versus 73.51 [SD ± 9.23] years), had a higher proportion of women (81% versus 68%, RR 1.18 [95% CI 1.13–1.24], and were more comorbid (mean CCI 2.68 [95% CI 2.47–2.88] versus 1.98 [95% CI 1.93–2.02]) compared to alendronate initiators. In addition, denosumab users had a higher prevalence of previous fractures (64% versus 46%, RR 1.38 [95% CI 1.28–1.48]). The adjusted HR for any MOF after treatment initiation with denosumab was 0.89 (95% CI 0.78–1.02) compared to initiation with alendronate.ConclusionThe risk of incident MOF among subjects with diabetes was similar between those initially treated with alendronate and denosumab. These findings indicate that the two treatment strategies are equally effective in preventing osteoporotic fractures in subjects with diabetes.
Highlights
Osteoporosis is an emerging global health problem characterized by microarchitectural deterioration of bone tissue with increased bone fragility and higher fracture risk leading to increased morbidity and mortality [1,2,3]
Subjects initiated with denosumab were older, mean ( ± standard deviations (SD)) 75.60 ( ± 9.72) versus 73.51 ( ± 9.23) years (p < 0.001), had a higher proportion of women in the cohort (81% versus 68%, risk ratios (RR) 1.18 [95% confidence intervals (CI) 1.13–1.24), and were more comorbid compared to alendronate initiators
There was no difference in marital status or income, either on total income or within each quintile, between subjects initiated with alendronate and denosumab
Summary
Osteoporosis is an emerging global health problem characterized by microarchitectural deterioration of bone tissue with increased bone fragility and higher fracture risk leading to increased morbidity and mortality [1,2,3]. Diabetes mellitus is a chronic metabolic imbalance associated with increased risk of fractures that cannot be sufficiently predicted by reduced bone mineral density (BMD) [4, 5]. In patients with type 1 and type 2 diabetes, the fracture risk may be increased by 7- and 1.3-fold, respectively [4]. A current meta-analysis found a relative risk of hip fracture of 4.93 in type 1 diabetes and 1.33 in type 2 diabetes [6]. The relative risk of non-vertebral fractures was found increased by 1.92 and 1.19 in type 1 and type 2 diabetes, respectively [6]. Compromised insulin pathways are assumed to cause a deficit in bone structure, reduced osteoblast activity, and a lower number of osteoclasts [8]
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